NPASS Compound

Natural Product: NPC20339

Natural Product ID	NPC20339
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Donnaienin
IUPAC Name	(2S)-2-methyl-4-[(2R,8S,11S)-2,8,11-trihydroxy-11-[(2R,3R,5S)-3-hydroxy-5-[(1S)-1-hydroxypentadecyl]oxolan-2-yl]undecyl]-2H-furan-5-one
Synonyms	Donnaienin
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL443448
PubChem CID	21600039
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0003909] Fatty Acyls [CHEMONTID:0001334] Fatty alcohols [CHEMONTID:0002518] Annonaceous acetogenins

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

Chemical Representations

RDKit 3D 107108 0 0 0 0 0 0 0 0999 V2000 12.3600 1.1697 -3.9761 C 0 0 0 0 0 0 0 0 0 0 0 0 10.8852 1.5275 -3.8541 C 0 0 0 0 0 0 0 0 0 0 0 0 10.2683 0.6635 -2.7756 C 0 0 0 0 0 0 0 0 0 0 0 0 10.3688 -0.7930 -3.0757 C 0 0 0 0 0 0 0 0 0 0 0 0 9.7544 -1.6679 -1.9954 C 0 0 0 0 0 0 0 0 0 0 0 0 10.4207 -1.4801 -0.6769 C 0 0 0 0 0 0 0 0 0 0 0 0 9.8798 -2.2900 0.4482 C 0 0 0 0 0 0 0 0 0 0 0 0 8.4197 -2.0232 0.7550 C 0 0 0 0 0 0 0 0 0 0 0 0 8.2871 -0.5650 1.0769 C 0 0 0 0 0 0 0 0 0 0 0 0 6.8519 -0.2128 1.4274 C 0 0 0 0 0 0 0 0 0 0 0 0 6.4236 -0.9634 2.6422 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0096 -0.5889 3.0137 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0633 -0.9622 1.9346 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6197 -0.6225 2.1995 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3165 0.8223 2.3444 C 0 0 1 0 0 0 0 0 0 0 0 0 0.8582 1.0560 2.6165 C 0 0 2 0 0 0 0 0 0 0 0 0 0.4139 0.6182 3.9939 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1138 0.7818 3.7938 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.2399 0.3850 2.3792 C 0 0 2 0 0 0 0 0 0 0 0 0 0.0065 0.3579 1.7733 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.1550 1.2410 1.5231 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.5140 1.3659 2.0683 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4465 2.2232 1.2971 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7932 1.8184 -0.0991 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.4228 0.4560 -0.0400 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.8322 -0.0893 -1.3865 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.4711 -1.4371 -1.1197 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.9666 -2.1591 -2.2974 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.9365 -1.5632 -3.2181 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.2613 -1.1035 -2.7561 C 0 0 2 0 0 0 0 0 0 0 0 0 -9.3098 -0.0063 -1.7600 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.7100 0.3835 -1.3899 C 0 0 0 0 0 0 0 0 0 0 0 0 -11.8233 -0.1231 -1.8478 C 0 0 0 0 0 0 0 0 0 0 0 0 -12.9748 0.5499 -1.2151 C 0 0 1 0 0 0 0 0 0 0 0 0 -12.4439 1.5089 -0.3746 O 0 0 0 0 0 0 0 0 0 0 0 0 -11.0709 1.4336 -0.4406 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.2211 2.1398 0.1996 O 0 0 0 0 0 0 0 0 0 0 0 0 -13.8709 1.1115 -2.3068 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.0331 -2.1998 -2.2727 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.7372 1.9227 -0.9409 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.1717 0.5497 0.2856 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.3646 2.1151 4.0735 O 0 0 0 0 0 0 0 0 0 0 0 0 3.0513 1.5260 3.2705 O 0 0 0 0 0 0 0 0 0 0 0 0 12.5142 0.3204 -4.6878 H 0 0 0 0 0 0 0 0 0 0 0 0 12.8910 2.0746 -4.3432 H 0 0 0 0 0 0 0 0 0 0 0 0 12.7443 0.8439 -2.9996 H 0 0 0 0 0 0 0 0 0 0 0 0 10.8437 2.5994 -3.5771 H 0 0 0 0 0 0 0 0 0 0 0 0 10.3349 1.3736 -4.7886 H 0 0 0 0 0 0 0 0 0 0 0 0 9.1742 0.9183 -2.7597 H 0 0 0 0 0 0 0 0 0 0 0 0 10.6669 0.9638 -1.7952 H 0 0 0 0 0 0 0 0 0 0 0 0 9.8691 -1.0030 -4.0467 H 0 0 0 0 0 0 0 0 0 0 0 0 11.4532 -1.0557 -3.1229 H 0 0 0 0 0 0 0 0 0 0 0 0 8.6584 -1.6005 -1.9571 H 0 0 0 0 0 0 0 0 0 0 0 0 9.9687 -2.7254 -2.3316 H 0 0 0 0 0 0 0 0 0 0 0 0 10.4008 -0.4108 -0.3766 H 0 0 0 0 0 0 0 0 0 0 0 0 11.5226 -1.7278 -0.7399 H 0 0 0 0 0 0 0 0 0 0 0 0 10.0519 -3.3733 0.3700 H 0 0 0 0 0 0 0 0 0 0 0 0 10.4479 -1.9629 1.3675 H 0 0 0 0 0 0 0 0 0 0 0 0 8.2032 -2.6279 1.6702 H 0 0 0 0 0 0 0 0 0 0 0 0 7.7421 -2.3621 -0.0267 H 0 0 0 0 0 0 0 0 0 0 0 0 8.9347 -0.2334 1.8928 H 0 0 0 0 0 0 0 0 0 0 0 0 8.4910 0.0170 0.1256 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2659 -0.4205 0.5103 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8400 0.8767 1.6778 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1236 -0.6534 3.4686 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4617 -2.0650 2.5202 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0462 0.4917 3.2727 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6884 -1.1140 3.9501 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3364 -0.5663 0.9273 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0938 -2.0900 1.8557 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2472 -1.2134 3.0488 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0502 -0.9797 1.2919 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5127 1.3735 1.3566 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6725 2.1601 2.5489 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7644 1.2818 4.7923 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6266 -0.4458 4.1481 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6032 0.1251 4.5332 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6703 -0.6535 2.3500 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7310 2.2330 1.3064 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9912 0.3544 2.1984 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4479 1.8559 3.1003 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0887 3.3015 1.3289 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4531 2.3122 1.8259 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6168 2.5689 -0.4031 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7494 -0.2880 0.4238 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3003 0.5092 0.6599 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4382 0.5772 -1.9938 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8821 -0.2914 -1.9559 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5916 -2.1100 -0.7292 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.1190 -1.4324 -0.2344 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4561 -3.1149 -1.8947 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0758 -2.6064 -2.8514 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.1561 -2.3797 -4.0036 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4901 -0.7605 -3.8791 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.8289 -0.7262 -3.6641 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.7897 -0.1724 -0.8207 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.8592 0.9389 -2.1917 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.9258 -0.9371 -2.6058 H 0 0 0 0 0 0 0 0 0 0 0 0 -13.5608 -0.1625 -0.5780 H 0 0 0 0 0 0 0 0 0 0 0 0 -14.3919 2.0162 -1.9957 H 0 0 0 0 0 0 0 0 0 0 0 0 -13.2553 1.2456 -3.2029 H 0 0 0 0 0 0 0 0 0 0 0 0 -14.6167 0.3076 -2.5278 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.3438 -2.6661 -3.0853 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9804 2.3465 -1.8138 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3068 0.1122 0.1261 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8861 2.1585 4.9077 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5896 1.7975 4.0804 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 14 15 1 0 15 16 1 0 16 17 1 0 17 18 1 0 18 19 1 0 19 20 1 0 19 21 1 0 21 22 1 0 22 23 1 0 23 24 1 0 24 25 1 0 25 26 1 0 26 27 1 0 27 28 1 0 28 29 1 0 29 30 1 0 30 31 1 0 31 32 1 0 32 33 2 0 33 34 1 0 34 35 1 0 35 36 1 0 36 37 2 0 34 38 1 0 30 39 1 0 24 40 1 0 21 41 1 0 18 42 1 0 15 43 1 0 20 16 1 0 36 32 1 0 1 44 1 0 1 45 1 0 1 46 1 0 2 47 1 0 2 48 1 0 3 49 1 0 3 50 1 0 4 51 1 0 4 52 1 0 5 53 1 0 5 54 1 0 6 55 1 0 6 56 1 0 7 57 1 0 7 58 1 0 8 59 1 0 8 60 1 0 9 61 1 0 9 62 1 0 10 63 1 0 10 64 1 0 11 65 1 0 11 66 1 0 12 67 1 0 12 68 1 0 13 69 1 0 13 70 1 0 14 71 1 0 14 72 1 0 15 73 1 6 16 74 1 1 17 75 1 0 17 76 1 0 18 77 1 1 19 78 1 1 21 79 1 6 22 80 1 0 22 81 1 0 23 82 1 0 23 83 1 0 24 84 1 6 25 85 1 0 25 86 1 0 26 87 1 0 26 88 1 0 27 89 1 0 27 90 1 0 28 91 1 0 28 92 1 0 29 93 1 0 29 94 1 0 30 95 1 6 31 96 1 0 31 97 1 0 33 98 1 0 34 99 1 1 38100 1 0 38101 1 0 38102 1 0 39103 1 0 40104 1 0 41105 1 0 42106 1 0 43107 1 0 M END

Standard InCHIKey	JTTZQARJVXNGRN-PSLIAIELSA-N
Standard InCHI	InChI=1S/C35H64O8/c1-3-4-5-6-7-8-9-10-11-12-13-17-20-30(38)33-25-32(40)34(43-33)31(39)22-21-28(36)18-15-14-16-19-29(37)24-27-23-26(2)42-35(27)41/h23,26,28-34,36-40H,3-22,24-25H2,1-2H3/t26-,28-,29+,30-,31-,32+,33-,34+/m0/s1
SMILES	CCCCCCCCCCCCCC[C@@H]([C@@H]1C[C@H]([C@H](O1)[C@H](CC[C@H](CCCCC[C@H](CC1=C[C@@H](OC1=O)C)O)O)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	612.46	Volume:	661.852 ? Van der Waals volume.
Dense:	0.925	LogP:	4.399 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.076 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.093 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	26.0	Rigid Bonds:	11.0
TPSA:	136.68 ? Topological Polar Surface Area.	H-Bond Acceptor:	8.0
H-Bond Donor:	5.0	Rings:	2.0
Heavy Atoms:	8.0

MedChem Properties

QED Drug-Likeness Score:	0.059	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.789	Fsp³:	0.914
MCE-18:	34.388 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Accepted	BMS Rule:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.869	Fluc inhibitor:	0.02 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.076 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.003 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.405	Promiscuous compounds:	0.314

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.276	MDCK Permeability:	-4.895
Pgp-inhibitor:	0.0	Pgp-substrate:	0.952
PAMPA:	0.722 ? The experimental data for Peff was logarithmically transformed (logPeff). Molecules with log Peff values below 2.0 were classified as low-permeability (Category 0), while those with log Peff values exceeding 2.5 were classified as high-permeability (Category 1).	Human Intestinal Absorption (HIA):	0.041
20% Bioavailability (F20%):	0.998	30% Bioavailability (F30%):	1.0
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.834
Plasma Protein Binding (PPB):	97.069%	Volume Distribution (VD):	0.509
Fu:	2.973% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.834
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.693
BSEP inhibitor:	0.896

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.004
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.001
CYP2C9-inhibitor:	0.001	CYP2C9-substrate:	0.003
CYP2D6-inhibitor:	0.002	CYP2D6-substrate:	0.303
CYP3A4-inhibitor:	0.001	CYP3A4-substrate:	0.964
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.978
HLM stability:	0.032 ? Human liver microsomal (HLM) stability. Category 0: stable+ (HLM > 30 min); Category 1: unstable- (HLM ≤ 30 min). The output value is the probability of human liver microsomal instability, where a value closer to 1 indicates a higher likelihood of instability.

ADMET: Excretion

Clearance (CL):

5.812

Half-life (T1/2):

1.289

ADMET: Toxicity

hERG Blockers:	0.34	hERG Blockers (10um):	0.805
Human Hepatotoxicity (H-HT):	0.699	Drug-induced Liver Injury (DILI):	0.214
AMES Toxicity:	0.172	Rat Oral Acute Toxicity:	0.049
Maximum Recommended Daily Dose:	0.962	Skin Sensitization:	1.0
Carcinogencity:	0.491	Eye Corrosion:	0.006
Eye Irritation:	0.864	Respiratory Toxicity:	0.968
Drug-induced Neurotoxicity:	0.16	Ototoxicity:	0.909
Hematotoxicity:	0.158	Drug-induced Nephrotoxicity:	0.98
Genotoxicity:	0.0	RPMI-8226 Immunitoxicity:	0.089
A549 Cytotoxicity:	0.953	Hek293 Cytotoxicity:	0.199
BCF:	1.265 ? Bioconcentration factors are used for considering secondary poisoning potential and assessing risks to human health via the food chain. The unit is -log10[(mg/L)/(1000*MW)].	IGC50:	4.889 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.074 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.886 ? 96 hour fathead minnow LC50. The unit of LC50FM is -log10[(mg/L)/(1000*MW)].

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO9339	Beilschmiedia tsangii	Species	Lauraceae	Eukaryota	n.a.	root	n.a.	PMID[21846089]
NPO9339	Beilschmiedia tsangii	Species	Lauraceae	Eukaryota	roots	Mudan, Pingtung County, Taiwan	2009-APR	PMID[21846089]
NPO9339	Beilschmiedia tsangii	Species	Lauraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]

Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

NP Quantity Composition/Concentration

Organism ID	Organism Name	Organism Material Preparation	Organism Part	NP Quantity (Standard)	NP Quantity (Minimum)	NP Quantity (Maximum)	Quantity Unit	Reference

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

Biological Activity

Activity Type	# Activity
IC50	6

Activity Type	# Activity
Cell line	5
Non-molecular	1

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT91	Cell line	KB	Homo sapiens	IC50	>	10.0	ug.mL-1	PMID[10096871]
NPT180	Cell line	HCT-8	Homo sapiens	IC50	>	10.0	ug.mL-1	PMID[9548832]
NPT180	Cell line	HCT-8	Homo sapiens	IC50	=	6.6	ug.mL-1	PMID[10096871]
NPT181	Cell line	Bel-7402	Homo sapiens	IC50	=	6.7	ug.mL-1	PMID[10096871]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	6.7	ug.mL-1	PMID[9548832]

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

Experimental ADME

Experiment Model	Experiment Tissue	ADME Type	ADME Relation	ADME Value	ADME Unit	Reference

Experimental Toxicity

Quantitative toxicity

Experiment Model	Experiment Organism	Toxicity Type	Toxicity Relation	Toxicity Value	Toxicity Unit	Reference

Common Abbreviations:
LC: Lethal Concentration; LD: Lethal Dose; LT:Lethal Time; NOAEL: No-observed-adverse-effect Level; BMDL: Benchmark Dose Lower Confidence Limit; BMD: Benchmark Dose; BMC:Benchmark Concentration; LOAEL: Lowest Observed Adverse Effect Level; RfD:Reference Dose; RfC:Reference Concentration; MRL: Minimal Risk Level; MEG: Maximum Exposure Guideline; PAC: Protective Action Criteria

Categorical toxicity labels

Hepatotoxicity	Carcinogenicity	Mutagenicity	Cardiotoxicity	Respiratory Toxicity	Eye Irritation	Endocrine Disruption

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP toxicity records from domain-specific databases. These databases include:
☉ ToxValDB: a curated database that compiles quantitative toxicity values for chemicals from diverse public sources to support toxicological research and risk assessment.
☉ TOXRIC: a comprehensive, free-to-access, online database providing toxicological/feature data. The toxicity labels are retrieved from this database. [PMID: 36400569]

Chemically structural similarity

Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes approximately 50,000 NPs with experimentally-derived bioactivity available in NPASS)

Similarity is measured using the Tanimoto coefficient (Tc) , which compares the binary fingerprints of two molecules. Tc is calculated as the intersection divided by the union of '1' bits in the fingerprints, ranging from 0 to 1, with 1 indicating highest similarity.

● The left chart: Distribution of similarity level between NPC20339 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	18365
0.1-0.2	29147
0.2-0.3	2057
0.3-0.4	75
0.4-0.5	32
0.5-0.6	70
0.6-0.7	74
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.78	Intermediate Similarity	NPC232555
0.78	Intermediate Similarity	NPC171174
0.78	Intermediate Similarity	NPC114694
0.78	Intermediate Similarity	NPC485248
0.78	Intermediate Similarity	NPC142117
0.78	Intermediate Similarity	NPC480249
0.78	Intermediate Similarity	NPC485249
0.78	Intermediate Similarity	NPC240695
0.7647	Intermediate Similarity	NPC488632
0.76	Intermediate Similarity	NPC473669
0.74	Intermediate Similarity	NPC107986
0.74	Intermediate Similarity	NPC223871
0.74	Intermediate Similarity	NPC231009
0.74	Intermediate Similarity	NPC103284
0.74	Intermediate Similarity	NPC110710
0.74	Intermediate Similarity	NPC1083
0.74	Intermediate Similarity	NPC82795
0.74	Intermediate Similarity	NPC286338
0.74	Intermediate Similarity	NPC603931
0.74	Intermediate Similarity	NPC604237
0.7358	Intermediate Similarity	NPC42598
0.7321	Intermediate Similarity	NPC239517
0.7308	Intermediate Similarity	NPC47937
0.7255	Intermediate Similarity	NPC488253
0.7255	Intermediate Similarity	NPC488251
0.72	Intermediate Similarity	NPC606043
0.717	Intermediate Similarity	NPC280621
0.717	Intermediate Similarity	NPC48338
0.717	Intermediate Similarity	NPC488628
0.7115	Intermediate Similarity	NPC182383
0.7021	Intermediate Similarity	NPC608138
0.6981	Remote Similarity	NPC93794
0.6981	Remote Similarity	NPC473504
0.6981	Remote Similarity	NPC81778
0.6981	Remote Similarity	NPC40066
0.6792	Remote Similarity	NPC81045
0.6792	Remote Similarity	NPC39754
0.6792	Remote Similarity	NPC171135
0.6792	Remote Similarity	NPC61257
0.6792	Remote Similarity	NPC320569
0.6792	Remote Similarity	NPC133730
0.6792	Remote Similarity	NPC191929
0.6792	Remote Similarity	NPC100454
0.6792	Remote Similarity	NPC242364
0.6792	Remote Similarity	NPC172821
0.6792	Remote Similarity	NPC274446
0.6792	Remote Similarity	NPC485251
0.6792	Remote Similarity	NPC151403
0.6792	Remote Similarity	NPC261952
0.6792	Remote Similarity	NPC605171
0.6727	Remote Similarity	NPC178215
0.6667	Remote Similarity	NPC134865
0.6667	Remote Similarity	NPC103523
0.6667	Remote Similarity	NPC112685
0.6667	Remote Similarity	NPC488627
0.6667	Remote Similarity	NPC488631
0.6607	Remote Similarity	NPC20621
0.6607	Remote Similarity	NPC318963
0.6607	Remote Similarity	NPC488250
0.6607	Remote Similarity	NPC605101
0.6491	Remote Similarity	NPC69082
0.6491	Remote Similarity	NPC488249
0.6481	Remote Similarity	NPC156804
0.6429	Remote Similarity	NPC473687
0.6429	Remote Similarity	NPC204686
0.6429	Remote Similarity	NPC219498
0.6429	Remote Similarity	NPC308412
0.6429	Remote Similarity	NPC134885
0.6429	Remote Similarity	NPC488247
0.6429	Remote Similarity	NPC210218
0.6429	Remote Similarity	NPC488248
0.6364	Remote Similarity	NPC477011
0.6316	Remote Similarity	NPC602738
0.6271	Remote Similarity	NPC233551
0.6271	Remote Similarity	NPC40376
0.6271	Remote Similarity	NPC21208
0.6207	Remote Similarity	NPC473478
0.6207	Remote Similarity	NPC473651
0.6207	Remote Similarity	NPC66346
0.614	Remote Similarity	NPC132940
0.6111	Remote Similarity	NPC100921
0.6111	Remote Similarity	NPC475159
0.6111	Remote Similarity	NPC131002
0.6111	Remote Similarity	NPC473780
0.6111	Remote Similarity	NPC477018
0.6111	Remote Similarity	NPC604521
0.6102	Remote Similarity	NPC231096
0.6102	Remote Similarity	NPC475581
0.6102	Remote Similarity	NPC283085
0.6102	Remote Similarity	NPC169511
0.6102	Remote Similarity	NPC62118
0.6102	Remote Similarity	NPC287164
0.6102	Remote Similarity	NPC234077
0.6102	Remote Similarity	NPC132496
0.6102	Remote Similarity	NPC107717
0.6102	Remote Similarity	NPC130359
0.6102	Remote Similarity	NPC488252
0.6102	Remote Similarity	NPC14901
0.6102	Remote Similarity	NPC606740
0.6102	Remote Similarity	NPC608614
0.6034	Remote Similarity	NPC20533
0.6034	Remote Similarity	NPC134807
0.6	Remote Similarity	NPC488623
0.6	Remote Similarity	NPC488624
0.6	Remote Similarity	NPC488629
0.5965	Remote Similarity	NPC480079
0.5806	Remote Similarity	NPC488630
0.5806	Remote Similarity	NPC488625
0.5806	Remote Similarity	NPC91067
0.5806	Remote Similarity	NPC488626
0.5789	Remote Similarity	NPC473649
0.5789	Remote Similarity	NPC473156
0.5789	Remote Similarity	NPC154097
0.5789	Remote Similarity	NPC488246
0.5789	Remote Similarity	NPC159750
0.5789	Remote Similarity	NPC73248
0.5789	Remote Similarity	NPC282815
0.5789	Remote Similarity	NPC480080
0.5789	Remote Similarity	NPC470401
0.5789	Remote Similarity	NPC600956
0.5789	Remote Similarity	NPC610454
0.5763	Remote Similarity	NPC329838
0.569	Remote Similarity	NPC473671
0.569	Remote Similarity	NPC475268
0.569	Remote Similarity	NPC470400
0.569	Remote Similarity	NPC77871
0.569	Remote Similarity	NPC9678
0.569	Remote Similarity	NPC319036
0.569	Remote Similarity	NPC604764
0.569	Remote Similarity	NPC605867
0.5667	Remote Similarity	NPC473707
0.5625	Remote Similarity	NPC473663
0.5625	Remote Similarity	NPC473723
0.5625	Remote Similarity	NPC475173
0.5574	Remote Similarity	NPC258068
0.5574	Remote Similarity	NPC476583
0.5556	Remote Similarity	NPC73310
0.5556	Remote Similarity	NPC473529
0.5556	Remote Similarity	NPC180363
0.5556	Remote Similarity	NPC94875
0.5556	Remote Similarity	NPC11332
0.5556	Remote Similarity	NPC480081
0.5556	Remote Similarity	NPC145914
0.5556	Remote Similarity	NPC601174
0.5556	Remote Similarity	NPC601403
0.5556	Remote Similarity	NPC603568
0.5556	Remote Similarity	NPC604330
0.5556	Remote Similarity	NPC608300
0.5556	Remote Similarity	NPC611200
0.5556	Remote Similarity	NPC611571
0.5517	Remote Similarity	NPC163093
0.55	Remote Similarity	NPC309211
0.55	Remote Similarity	NPC477010
0.5484	Remote Similarity	NPC89001
0.5484	Remote Similarity	NPC477014
0.5484	Remote Similarity	NPC477013
0.5469	Remote Similarity	NPC473905
0.5455	Remote Similarity	NPC482766
0.5323	Remote Similarity	NPC120398
0.5323	Remote Similarity	NPC471567
0.5263	Remote Similarity	NPC25764
0.5263	Remote Similarity	NPC235809
0.5263	Remote Similarity	NPC329829
0.5263	Remote Similarity	NPC39279
0.5263	Remote Similarity	NPC39167
0.5263	Remote Similarity	NPC292809
0.5263	Remote Similarity	NPC202055
0.5263	Remote Similarity	NPC606804
0.5263	Remote Similarity	NPC607425
0.5263	Remote Similarity	NPC608574
0.5224	Remote Similarity	NPC279267
0.5167	Remote Similarity	NPC241360
0.5167	Remote Similarity	NPC293136
0.5082	Remote Similarity	NPC473904
0.5079	Remote Similarity	NPC488244

Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

● The left chart: Distribution of similarity level between NPC20339 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6538
0.1-0.2	2571
0.2-0.3	41
0.3-0.4	0
0.4-0.5	0
0.5-0.6	0
0.6-0.7	0
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
		NPD

Bioactivity similarity

Similar Natural Products in NPASS

Similarity level is defined by Bioactivity similarity was calculated based on bioactivity descriptors of compounds. The bioactivity descriptors were calculated by a recently developed AI algorithm Chemical Checker (CC) [Nature Biotechnology, 38:1087–1096, 2020; Nature Communications, 12:3932, 2021], which evaluated bioactivity similarities at five levels:
☉ A: chemistry similarity;
☉ B: biological targets similarity;
☉ C: networks similarity;
☉ D: cell-based bioactivity similarity;
☉ E: similarity based on clinical data.
Those 5 categories of CC bioactivity descriptors were calculated and then subjected to manifold projection using UMAP algorithm, to project all NPs on a 2-Dimensional space. The current NP was highlighted with a small circle in the 2-D map. Below figures: left-to-right, A-to-E.

A: chemistry similarity

B: biological targets similarity

C: networks similarity

D: cell-based bioactivity similarity

E: similarity based on clinical data